This is a modular, phase I, two part, open-label, multicentre study of ceralasertib,
administered orally, in combination with cytotoxic chemotherapy regimens and/or novel
anti-cancer agents, to patients with advanced/metastatic solid malignancies. The study design
allows an escalation of the dose of ceralasertib in combination with the standard dose and
schedule of either cytotoxic chemotherapies and/or novel anti-cancer agents, with intensive
safety monitoring to ensure the safety of the patients. There are two parts to each
combination module of this study; part A, dose escalation and an optional part B, cohort
expansions in particular patient groups. The initial combination module will be with
Carboplatin (module 1). The second combination will be with Olaparib (module 2). The third
combination will be with durvalumab (module 3). The option to start further combination
modules will be the decision of the Safety Review Committee (SRC), based on emerging
preclinical data and, safety and tolerability information from the initial combination.
Combinations of ceralasertib with novel anti-cancer agents may also be explored. Once a
minimally biologically active dose of ceralasertib, for that combination module, has been
identified from part A of that module, the SRC may decide to commence part B if deemed to be
necessary. This may include cohort expansions of specific patient groups to explore
preliminary anti-tumour activity or the effect of food or particular drug combinations on
drug pharmacokinetics.
Principal Inclusion criteria:
- Aged at least 18
- The presence of a solid malignant tumour that is not considered appropriate for
further standard treatment
- Module 1 and 2 Part B study expansions, and Module 3: patients must have a tumour at
least 1 cm in size that can be measured using a CT or MRI scan
- Module 1 Part B Study expansion: second line lung adenocarcinoma with ATM deficient
tumours.
- Module 2 Part B All - No previous treatment with PARP inhibitor.
- Module 2 Part B1 Study expansion: advanced gastric adenocarcinoma (including GEJ)
patients with ATM deficient tumours
- Module 2 Part B2 Study expansion: advanced gastric adenocarcinoma (including GEJ)
patients with ATM proficient tumours
- Module2 Part B3 Study expansion: Second or thrid line HER2 negative breast cancer
- Module 2 Part B4 Study expansion: Second or third line triple negative breast cancer
(TNBC)
- Module 2 Part B5 Study expansion: BRCA mutant or RAD51C/D mutant or HRD positive
status ovarian cancer patient who are Platinum sensitive and have previously
progressed on a licensed PARPi
- Module 3: advanced recurrent or metastatic non-small cell lung cancer, or head and
neck squamous cell carcinoma
Principal exclusion criteria
- A diagnosis of ataxia telangiectasia
- Prior exposure to an ATR inhibitor
- Bad reaction to ceralasertib
- Module 1: Contra-indicated for treatment with carboplatin
- Module 2: Contra-indicated for treatment with olaparib
- Module 3: Contra-indicated for treatment with durvalumab